The ability of subpopulations of murine spleen cells to stimulate a mixed lymphocyte response (MLR) was studied. It was found that T cells and B cells were poor stimulators of an MLR across H-2 or Mls differences, while non-T, radiation resistant Ia positive splenic adherent cell (SAC) were 20-50 times more efficient as stimulators of these MLR's than unseparated spleen cells. These results suggest that Ia+SAC may be the predominant stimulating cells in spleen cell populations, and the preferential target for T cell recognition in cell interaction events. It has further been demonstrated that T cells responding to Mls determinants recognize such determinants in the context of "self" H-2 determinants. Studies employing K region mutants have investigated the influence of chimeric maturation environment upon the alloreactive T cell repertoire to mutant determinants, and suggest that this alloreactive repertoire is in fact influenced by the environment in which T cells mature.